Lymphokine activated killer activity results from 3 day incubation of human peripheral blood lymphocytes or murine splenocytes in recombinant interleukin 2 (rIL2). Human lymphokine activated killer (LAK) effector cells express natural killer (NK) cell markers such as CD16. Infusion of LAK cells with high doses of rIL2 has produced repression of some murine tumors and tumors in some patients. We have reported on the development of long-term cultures of LAK cells in rIL2 or OKT3 + rIL2. These result in a large increase in the number of cells and maintenance of LAK activity over 14- 21 days. LAK activity in these cultures can be further enhanced by the addition of beta IL1, IFN-beta or IFN-gamma. LAK effectors in these cultres are both CD16+, CD3- NK cells and CD3+, CD16-T cells. Initial data from murine experiments suggest that long-term LAK cells are at least as effective in vivo as short-term cells, with one experiment showing more effective activity on the part of long-term cells. Experiments proposed will further dissect the populations which develop LAK activity and identify the signals required for the optimal expression and maintenance of this function. Long-term LAK cells and subpopulations expressing LAK function will be tested in vivo to assess their therapeutic relevance. Availability of large numbers of cells highly enriched for LAK activity will allow us to test whether the dose of rIL2 can be reduced by increasing the number of activity of cells infused, resulting in reduction or elimination of tumor cells.